Overview

The purpose of this clinical trial is to determine whether silkworm pupa powder is effective in treating Alzheimer's disease. It will also investigate whether silkworm pupa powder can improve the nutritional and frailty status of patients with Dementia. The main questions it aims to answer are:

• Will silkworm pupa powder improve the daily living conditions of patients with Alzheimer's disease?
• Will silkworm pupa powder improve the nutritional status and frailty of Alzheimer's disease patients?

Researchers will compare silkworm pupa powder with a placebo (a similar substance containing 0.5% silkworm pupa powder) to see if silkworm pupa powder can treat Alzheimer's disease.

Participants will:

• Take silkworm pupa powder or placebo daily for four months;
• Visit the clinic for check-ups and tests every four weeks;
• Record their symptoms and various physiological indicators.

Eligibility

Inclusion Criteria:

• Diagnosis of probable Alzheimer's disease (AD) according to the National Institute on Aging-Alzheimer's Association (NIA-AA) criteria, with disease severity classified as mild, moderate, or severe (i.e., Mini-Mental State Examination [MMSE] total score between 0 and 24 points [inclusive] at screening and baseline).
• Confirmation of AD pathology per the 2024 revised AD diagnostic criteria (biomarker-defined AD with both Aβ and tau positivity):
• Aβ positivity: Plasma Aβ42/40 ratio ≤0.08 or amyloid-PET positivity (SUVR ≥1.1).
• Tau positivity: Plasma p-tau217 ≥2.5 pg/mL or CSF p-tau181/Aβ42 ratio ≥0.02.
• Age: 50 to 90 years of age (inclusive), with at least a primary school education. Both males and females are eligible.
• Stable medication use: If receiving approved AD therapies (e.g., acetylcholinesterase inhibitors, GV-971, NMDA receptor antagonists), doses must remain stable for ≥12 weeks prior to baseline. Treatment-naïve participants are also eligible. All other non-AD-related permitted concomitant medications must remain stable for ≥4 weeks prior to baseline unless otherwise specified.
• Hachinski Ischemia Scale (HIS) total score ≤4.
• Geriatric Depression Scale-15 (GDS-15) total score ≤4.
• Neuroimaging evidence: Screening CT/MRI showing age-related brain changes or cerebral atrophy.
• Caregiver availability: Participant has a stable and reliable caregiver, as confirmed by the investigator.
• Informed consent: Written informed consent must be provided by the participant or, if the participant lacks decision-making capacity, by a legally authorized representative (in accordance with local laws, regulations, and customs). Participants agree to provide peripheral blood, stool, and urine samples during the study for biomarker analysis.

Exclusion Criteria:

• Diagnosis of dementia other than Alzheimer's disease (AD) or other central nervous system disorders.
• Unstable vital signs accompanied by abnormalities in cardiac, pulmonary, hepatic, renal, or other organ functions.
• Abnormally low folate and/or vitamin B12 levels, or evidence that hypothyroidism has caused or exacerbated the participant's dementia. Participants with abnormal syphilis test results.
• Patients with comorbid psychiatric disorders.
• Long-term alcoholism or substance abuse that may compromise the evaluation of treatment efficacy.
• Participants with intolerance or allergy to the study medications.
• Abnormalities detected on cranial MRI, including ischemic or hemorrhagic infarctions, hydrocephalus, or brain tumors.
• Diagnosis of clinically significant cardiovascular or cerebrovascular disease requiring treatment within 12 months or at present.
• Antibiotic use:
  1. Continuous antibiotic use for more than 10 days within 12 weeks prior to baseline.
  2. Anticipated need for antibiotic treatment exceeding 10 days during the study.
• Geriatric Depression Scale-15 (GDS-15) score >4 at screening.
• Any other inadequately controlled condition (e.g., cardiac, respiratory, renal, or gastrointestinal disorders affecting absorption, such as gastric cancer, gastric bypass surgery, or recurrent diarrhea) that may jeopardize participant safety or interfere with study assessments, as judged by the investigator.
• Participation in any clinical trial involving novel chemical entities for Alzheimer's disease (AD) within 6 months prior to screening, unless confirmed to have been in the placebo group.
• Clinically significant abnormalities in physical examination, vital signs, laboratory tests, or electrocardiogram (ECG) requiring further investigation, treatment, or posing risks to study procedures/safety.
• Participation in clinical trials involving therapeutic monoclonal antibodies, antibody-derived proteins, immunoglobulin therapy, or vaccines within 6 months prior to screening, unless confirmed to have been in the placebo group.
• Participation in clinical trials involving anti-amyloid therapies (including monoclonal antibodies or BACE inhibitors), unless confirmed to have received only placebo.
• Uncontrolled immune disorders requiring treatment with immunoglobulins, systemic monoclonal antibodies (or derivatives), systemic immunosuppressants, or plasmapheresis during the study.
• Participants with uncontrolled bleeding disorders, including platelet count <50,000 or INR >1.5 (for those not on anticoagulants, e.g., warfarin). Participants on anticoagulants must have optimized and stable dosing for ≥4 weeks prior to screening. Anticoagulated participants are excluded from cerebrospinal fluid (CSF) assessments.